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A phase II study of lapatinib for brain metastases in patients with HER2-overexpressing breast cancer following trastuzumab based systemic therapy and cranial radiotherapy: subset analysis of Japanese patients

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Abstract

Background

It is known that one third of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer (MBC) treated with trastuzumab will develop brain metastases. As the development of brain metastases is fatal, controlling its progression is clinically meaningful. However, effective therapy for MBC patients with brain metastasis after cranial radiation is limited. The international clinical study in which six Japanese patients participated indicated the antitumor activity of lapatinib against brain metastases of HER2-overexpressing breast cancer.

Methods

The efficacy, safety, and pharmacokinetics of lapatinib 750 mg given twice daily to Japanese HER2-overexpressing MBC patients with brain metastases were assessed as part of the international clinical study.

Results

Of six Japanese patients treated in this study, two patients had shown volumetric reduction >20 % in their central nervous system (CNS), one of whom had >50 % reduction. Three patients, including two of these patients, had shown >20 % volumetric reduction in non-CNS lesions. Frequently reported adverse events were diarrhea and rash, all of which were controllable. The AUC0–12 of lapatinib on day 28 was 1.74 times higher than that on day 1.

Conclusion

These results suggest that lapatinib monotherapy 750 mg given twice daily can exert some efficacy and has potential as a clinically meaningful treatment option for Japanese HER2-overexpressing breast cancer patients with brain metastases after cranial radiation.

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Acknowledgments

We thank the women who participated in these studies and their families. The authors also acknowledge the dedicated work of all the research nurses and study coordinators at the study centers. This work was sponsored by GlaxoSmithKline K.K.

Conflict of interest

All authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Hiroji Iwata

  2. Department of Palliative Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Masaru Narabayashi

  3. Department of Oncology, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Yoshinori Ito

  4. Clinical Research Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Shigehira Saji

  5. Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yasuhiro Fujiwara

  6. Development and Medical Affairs Division, GlaxoSmithKline K.K., 4-6-15 Sendagaya, Shibuya-ku, Tokyo, 151-8566, Japan

    Shigeyuki Usami & Koichi Katsura

  7. Department of Medical Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Shigehira Saji & Yasutsuna Sasaki

Authors
  1. Hiroji Iwata
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  2. Masaru Narabayashi
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  3. Yoshinori Ito
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  4. Shigehira Saji
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  5. Yasuhiro Fujiwara
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  6. Shigeyuki Usami
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  7. Koichi Katsura
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  8. Yasutsuna Sasaki
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Corresponding author

Correspondence to Hiroji Iwata.

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Iwata, H., Narabayashi, M., Ito, Y. et al. A phase II study of lapatinib for brain metastases in patients with HER2-overexpressing breast cancer following trastuzumab based systemic therapy and cranial radiotherapy: subset analysis of Japanese patients. Int J Clin Oncol 18, 621–628 (2013). https://doi.org/10.1007/s10147-012-0444-2

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  • DOI: https://doi.org/10.1007/s10147-012-0444-2

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